Sodium benzoate is a widely used preservative found in many foods and soft drinks. It is metabolized within mitochondria to produce hippurate, which is then cleared by the kidneys. We previously reported that ingestion of
sodium benzoate at the generally regarded as safe (GRAS) dose leads to a robust excursion in the plasma
hippurate level [1]. Since previous reports demonstrated adverse effects of benzoate and hippurate on glucose
homeostasis in cells and in animal models, we hypothesized that benzoate might represent a widespread and underappreciated diabetogenic dietary exposure in humans. Here, we evaluated whether acute exposure to GRAS
levels of sodium benzoate alters insulin and glucose homeostasis through a randomized, controlled, cross-over
study of 14 overweight subjects. Serial blood samples were collected following an oral glucose challenge, in
the presence or absence of sodium benzoate. Outcome measurements included glucose, insulin, glucagon, as
well as temporal mass spectrometry-based metabolic profiles. We did not find a statistically significant effect
of an acute oral exposure to sodium benzoate on glucose homeostasis. Of the 146 metabolites targeted, four
changed significantly in response to benzoate, including the expected rise in benzoate and hippurate. In addition,
anthranilic acid, a tryptophan metabolite, exhibited a robust rise, while acetylglycine dropped. Although our
study shows that GRAS doses of benzoate do not have an acute, adverse effect on glucose homeostasis, future
studies will be necessary to explore the metabolic impact of chronic benzoate exposure.